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Medical use of squalene as a natural antioxidant

Yıl 2013, Cilt: 3 Sayı: 4, 220 - 228, 30.01.2014

Fatma Esra Güneş

Öz

The aim of the present review is to emphasize the importance of squalene, a nutrient, in preventive and therapeutic medicine. Squalene is a triterpene that carries oxygen independent of the hemoglobin and it can carry oxygen directly to cell membranes throughout the body and reach the regions having low oxygen supply. Squalene has been reported to have an inhibitory effect on cancer promotion and a high anti-tumor activity; thus, it is primarily used as a supportive therapy in a variety of cancers. Epidemiological and experimental animal researches regarding squalene’s anti-cancer properties are interesting and promising. However, these properties of squalene should be supported by further extensive trials in humans.


Key words: Squalene, triterpene, cytotoxic activity, anti-tumor activity, skin disease, cholesterol metabolism

Anahtar Kelimeler

Squalene triterpene cytotoxic activity anti-tumor activity skin disease cholesterol metabolismMÜSBED 2013;3(4):220-228Derleme / Review

Kaynakça

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  • Tuberoso CIG, Kowalczyk A, Sarritzu E, Cabras P. Determination of antioxidant compounds and antioxidant activity in commercial oilseeds for food use. Food Chem. 2007; 103: 1494-1501.
  • Koivisto PV, Miettinen TA. Increased amounts of cholesterol precursors in lipoproteins after ileal exclusion. Lipids. 1988; 23: 9939
  • Stewart ME. Sebaceous gland lipids. Semin Dermatol. 1992; 11: 100
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  • Mesa C, Fernandez LE. Challenges facing adjuvants for cancer immunotherapy. Immunol Cell Biol. 2004; 82: 644-650.
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Doğal bir antioksidan olarak skualenin medikal kullanımı

Yıl 2013, Cilt: 3 Sayı: 4, 220 - 228, 30.01.2014

Fatma Esra Güneş

Öz

Bu derlemenin amacı, koruyucu ve tedavi edici tıp içerisinde skualenin yerini ve önemini vurgulamaktır. Skualen bir triterpen olup, hemoglobinden bağımsız olarak oksijeni hücreye doğrudan taşıyarak tüm vücuda ulaştırabilmektedir. Skualenin kanser oluşumunu önlediği ve yüksek anti-tümör aktivitesine sahip olduğu bildirilmiştir, bu nedenle, çeşitli kanserlerin tedavi sürecinde destekleyici olarak kullanılabilmektedir. Skualenin bu konu ile ilgili epidemiyolojik ve deneysel hayvan araştırmaları ilginç ve umut vericidir. Bununla birlikte, skualenin kimyasal özellikleri nedeniyle farklı hastalıkların tedavisinde kullanılması açısından, insanlarda daha geniş çalışmalarla desteklenmesi gerekmektedir.


Anahtar Kelimeler : Skualen, triterpen, sitotoksik aktivite, anti-tümor aktivite, deri hastalıkları, kolesterol metabolizması

Anahtar Kelimeler

Skualen triterpen sitotoksik aktivite antitümor aktivite deri hastalıkları kolesterol metabolizması

Kaynakça

  • Heller JH, Pasternak VZ, Ransom JP, Heller MS, A new reticuloendothelial system stimulating agent (‘Restim’) from shark livers. Nature, 1963;199: 904-905.
  • Richter E & Schafer SG. Effect of squalane on hexachlorobenzene (HCB) concentrations in tissues of mice. J Environ Sci Health B. 1982; 17: 195-203.
  • Storm HM, Oh SY, Kimler BF, Norton, S. Radioprotection of mice by dietary squalene. Lipids. 1993; 28: 555-559.
  • Kohno Y, Egawa Y, Itoh S, Nagaoka S, Takahashi M, Mukai K. Kinetic study of quenching reaction of singlet oxygen and scavenging reaction of free radical by squalene in n-butanol. Biochim Biophys Acta. 1995; 1256: 52-56.
  • Liu GC, Ahrens EH Jr, Schreibman PH, Crouse JR. Measurement of squalene in human tissues and plasma: validation and application. J Lipid Res 1976; 17: 38-45.
  • Kelly GS. Squalene and its potential clinical uses. Altern Med Rev. 1999; 4: 29-36.
  • Spanova M, Daum G. Squalene – biochemistry, molecular biology, process biotechnology, and applications. Eur J Lipid Sci Technol. 2011; 113: 1299-1320.
  • Vazquez L, Fornari T, Senorans FJ, Reglero G, Torres CF. Supercritical carbon dioxide fractionation of nonesterified alkoxyglycerols obtained from shark liver oil. J Agric Food Chem. 2008; 56: 10781083.
  • Tuberoso CIG, Kowalczyk A, Sarritzu E, Cabras P. Determination of antioxidant compounds and antioxidant activity in commercial oilseeds for food use. Food Chem. 2007; 103: 1494-1501.
  • Koivisto PV, Miettinen TA. Increased amounts of cholesterol precursors in lipoproteins after ileal exclusion. Lipids. 1988; 23: 9939
  • Stewart ME. Sebaceous gland lipids. Semin Dermatol. 1992; 11: 100
  • Xu R, Fazio GC, Matsuda SP. () On the origins of triterpenoid skeletal diversity. Phytochemistry. 2004; 65: 261-291.
  • Slakey LL, Ness GC, Qureshi N, Porter JW. Occurrence of the enzymes effecting the conversion of acetyl CoA to squalene in homogenates of hog aorta. J Lipid Res. 1973; 14: 485-494.
  • Laaksonen R, Ojala JP, Tikkanen MJ, Himberg JJ. Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1994; 46: 313-317.
  • Reddy LH, Couvreur P. Squalene: A natural triterpene for use in disease management and therapy. Adv Drug Deliv Rev. 2009; 61: 1412-1426.
  • Miettinen TA, Vanhanen H. Serum concentration and metabolism of cholesterol during rapeseed oil and squalene feeding. Am J Clin Nutr. 1994; 59: 356-363.
  • Gylling H, Miettinen TA. Postabsorptive metabolism of dietary squalene. Atherosclerosis. 1994; 106: 169-178.
  • Spanova M, Czabany T, Zellnig G, Leitner E, Hapala I, Daum G. Effect of lipid particle biogenesis on the subcellular distribution of squalene in the yeast Saccharomyces cerevisiae. J Biol Chem. 2010; 285: 6127-6133.
  • Milla P, Athenstaedt K, Viola F, Oliaro-Bosso S, Kohlwein SD, Daum G, Balliano G. Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles. J Biol Chem. 2002; 277: 2406-2412.
  • Tilvis R, Kovanen PT, Miettinen TA. Metabolism of squalene in human fat cells. Demonstration of a two-pool system. J Biol Chem. 1982; 257: 10300-10305.
  • Kalvodova L. Squalene-based oil-in-water emulsion adjuvants perturb metabolism of neutral lipids and enhance lipid droplet formation. Biochem Biophys Res Commun. 2010; 393: 350-355.
  • Goodrum JF, Earnhardt TS, Goines ND, Bouldin TW. Lipid droplets in Schwann cells during tellurium neuropathy are derived from newly synthesized lipid. J Neurochem. 1990; 55: 1928-1932.
  • Asnis DS, Saltzman HP, Melchert A. Shark oil pneumonia. An overlooked entity. Chest. 1993; 103: 976-977.
  • Smith TJ. Squalene: potential chemopreventive agent. Expert Opin Invest. Drugs. 2000; 9: 1841-1848.
  • Peltola P, Pihlajamaki J, Koutnikova H, Ruotsalainen E, Salmenniemi U, Vauhkonen I, et al. Visceral obesity is associated with high levels of serum squalene. Obesity (Silver Spring). 2006; 14: 1155-1163.
  • Whittenton J, Harendra S, Pitchumani R, Mohanty K, Vipulanandan C, Thevananther S. Evaluation of asymmetric liposomal nanoparticles for encapsulation of polynucleotides. Langmuir. 2008; 24: 8533-8540.
  • Fox CB, Anderson RC, Dutill TS, GotoY, Reed SG, Vedvick, T. Monitoring the effects of component structure and source on formulation stability and adjuvant activity of oil-in-water emulsions. Colloids Surf B Biointerfaces. 2008; 65: 98-105.
  • Huang ZR, Lin YK, Fang JY. Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. Molecules. 2009; 14: 540-554.
  • Fox CB. Squalene emulsions for parenteral vaccine and drug delivery. Molecules.2009;14:3286-312.
  • Mesa C, Fernandez LE. Challenges facing adjuvants for cancer immunotherapy. Immunol Cell Biol. 2004; 82: 644-650.
  • Kim YJ, Kim TW, Chung H, Kwon IC, Sung HC, Jeong SY. The effects of serum on the stability and the transfection activity of the cationic lipid emulsion with various oils. Int J Pharm. 2003; 252: 241-252.
  • Wang JJ, Sung KC, Hu OY, Yeh CH, Fang JY. Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugs. J Contr. Release. 2006; 115: 140-149.
  • Allison AC, Byars NE. An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cellmediated immunity. J Immunol Methods 1986; 95: 157-168.
  • Hjorth RN. Adjuvants for Viral Vaccines. 1997, US Patent No: 5690942; available at http://www.patentstorm.us/patents/5690942/fulltext. html.
  • Hjorth RN. Adjuvants for Viral Vaccines. 1998, US Patent No: 5718904; available at http://www.patentstorm.us/patents/5718904/fulltext. html.
  • Del Giudice G, Fragapane E, Bugarini R, Hora M, Henriksson T, Palla E, et al. Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene. Clin Vaccine Immunol. 2006; 13: 101010
  • Suli J, Benisek Z, Elias D, Svrcek S, Ondrejkova A, Ondrejka R, et al. Experimental squalene adjuvant. I. Preparation and testing of its effectiveness. Vaccine. 2004; 22: 3464-3469.
  • Benisek Z, Suli J, Elias D, Lenhardt L, Ondrejkova A, Ondrejka R, et al. Experimental squalene adjuvant. II. Harmlessness and local reactogenity. Vaccine. 2004; 22: 3470-3474.
  • Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles T, Syrengelas A, et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma--long-term results of a clinical trial. Blood. 1997; 89: 3129-3135.
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  • Matyas GR, Rao M, Pittman PR, Burge R, Robbins IE, Wassef NM, et al. Detection of antibodies to squalene: III. Naturally occurring antibodies to squalene in humans and mice. J Immunol Methods. 2004; 286: 47-67.
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  • Willett WC. Diet and health: what should we eat? Science. 1994; 264: 532-5
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  • Castelli F, Sarpietro MG, Micieli D, Stella B, Rocco F, Cattel L. Enhancement of gemcitabine affinity for biomembranes by conjugation with squalene: differential scanning calorimetry and Langmuir-Blodgett studies using biomembrane models. J Colloid Interface Sci. 2007; 316: 43-52.
  • Pili B, Bourgaux C, Amenitsch H, Keller G, Lepêtre-Mouelhi S, Desmaële D, et al. Interaction of a new anticancer prodrug, gemcitabinesqualene, with a model membrane: coupled DSC and XRD study. Biochim Biophys Acta. 2010; 1798: 1522-1532.
  • Yarkoni E, Rapp HJ. Tumor regression after intralesional injection of mycobacterial components emulsified in 2,6,10,15,19,23-hexamethyl2,6,10,14,18,22-tetracosahexaene (squalene), 2,6,10,15, 19,23-hexamethyltetracosane (squalane), peanut oil, or mineral oil. Cancer Res. 1979; 39: 1518-1520.
  • Pimm MV, Baldwin RW, Lederer E. Suppression of an ascitic rat hepatoma with cord factor and Nocardia cell wall skeleton in squalene emulsions. Eur J Cancer. 1980; 16: 1645-1647.
  • Nakagawa M, Yamaguchi T, Fukawa H, Ogata J, Komiyama S, Akiyama S, Kuwano, M. Potentiation by squalene of the cytotoxicity of anticancer agents against cultured mammalian cells and murine tumor. Jpn J Cancer Res. 1985; 76: 315-320.
  • Das B, Yeger H, Baruchel H, Freedman MH, Koren G, Baruchel S. In vitro cytoprotective activity of squalene on a bone marrow versus neuroblastoma model of cisplatin-induced toxicity. implications in cancer chemotherapy. Eur J Cancer. 2003; 39: 2556-2565.
  • Das B, Antoon R, Tsuchida R, Lotfi S, Morozova O, Farhat W, et al. Squalene selectively protects mouse bone marrow progenitors against cisplatin and carboplatin-induced cytotoxicity in vivo without protecting tumor growth. Neoplasia. 2008; 10: 1105-1119.
  • Senthilkumar S, Devaki T, Manohar BM, Babu MS. Effect of squalene on cyclophosphamide-induced toxicity. Clin Chim Acta. 2006; 364: 335-3
  • Senthilkumar S, Yogeeta SK, Subashini R, Devaki, T. Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats. Chem Biol Interact. 2006; 160: 252-260.
  • Warleta F, Campos M, Allouche Y, Sánchez-Quesada C, Ruiz-Mora J, Beltrán G. Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDAMB-231 human breast cancer cells. Food Chem Toxicol. 2010; 48: 1092-1100.
  • Nowicki R, Baranska-Rybak W. Shark liver oil as a supporting therapy in atopic dermatitis. Pol Merkur Lekarski. 2007; 22: 312-313.
  • Newmark HL. Squalene, olive oil, and cancer risk: a review and hypothesis. Cancer Epidemiol Biomarkers Prev. 1997; 6: 1101-1103.
  • Hashim YZ, Eng M, Gill CI, McGlynn H, Rowland IR. Components of olive oil and chemoprevention of colorectal cancer. Nutr Rev. 2005; 63: 374-386.
  • Sabeena Farvin KH, Anandan R, Kumar SH, Shiny KS, Sankar TV, Thankappan TK. Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res. 2004; 50: 231-236.
  • Keller RK, Fliesler SJ. Incorporation of squalene into rod outer segments. J Biol Chem. 1990; 265: 13709-13712.
  • Newmark HL. Squalene, olive oil, and cancer risk. Review and hypothesis. Ann N Y Acad Sci. 1999; 889: 193-203.
  • Rao CV, Newmark HL, Reddy BS. Chemopreventive effect of squalene on colon cancer. Carcinogenesis. 1998; 19: 287-290.
  • Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D. Cancer and Mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev. 2000; 9: 869-873.
  • Aguilera Y, Dorado ME, Prada FA, Martinez JJ, Quesada A, RuizGutierrez V. The protective role of squalene in alcohol damage in the chick embryo retina. Exp Eye Res. 2005; 80: 535-543.
  • Motawi TM, Sadik NA, Refaat A. Cytoprotective effects of DL-alphalipoic acid or squalene on cyclophosphamide-induced oxidative injury: An experimental study on rat myocardium, testicles and urinary bladder. Food Cheml Toxicol. 2010; 48: 2326-2336.
  • Strandberg TE, Tilvis RS, Miettinen TA. Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment. J Lipid Res.1990; 31:1637-1643.
  • Richter E, Schafer SG. The effect of squalane on the absorption of dietary cholesterol by the rat. Res Exp Med (Berl). 1982; 180: 189-191.
  • Kritchevsky D, Moyer AW, Tesar WC, Logan JB, Brown RA, Richmond G. Squalene feeding in experimental atherosclerosis. Circ Res. 1954; 2: 340-343.
  • Chan P, Tomlinson B, Lee CB, Lee YS. Effectiveness and safety of lowdose pravastatin and squalene, alone and in combination, in elderly patients with hypercholesterolemia. J Clin Pharmacol. 1996; 36: 4224
  • Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell. 2006; 124: 35-46.
  • Janevski M, McGlynn M, Lewandowski P. Squalene supplementation alters genes associated with liver cholesterol metabolism. Asia Pac J Clin Nutr. 2006; 15:3, S105.
  • Farvin KHS, Anandan R, Kumar SHS, Shiny KS, Mathew S, Sankar TV, Nair PGV. Biochemical studies on thecardioprotective effect of squalene against isoprenaline-induced myocardial infarction in rats. Fishery Technology. 2009; 46: 139-151.
  • Bullon P, Quiles JL, Morillo JM, Rubini C, Goteri G, Granados-Principal S, Battino M, Ramirez-Tortosa M. Gingival vascular damage in atherosclerotic rabbits: hydroxytyrosol and squalene benefits. Food Chem Toxicol. 2009; 47: 2327-2331.
  • Liu Y, Xu X, Bi D, Wang X, Zhang X, Dai H. Influence of squalene feeding on plasma leptin, testosterone and blood pressure in rats. Indian J Med Res. 2009; 129: 150-153.
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  • Cho S, Choi CW, Lee DH, Won CH, Kim SM, Lee S, et al. High-dose squalene ingestion increases type I procollagen and decreases ultraviolet-induced DNA damage in human skin in vivo but is associated with transient adverse effects. Clin Exp Dermatol. 2009; 34: 500-50
  • Murakoshi M, Nishino H, Tokuda H, Iwashima A, Okuzumi J, Kitano H, Iwasaki,R. Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis. Int J Cancer. 1992; 52: 950-952.
  • Blasco L, Duracher L, Forestier JP. Skin constituents as cosmetic ingredients. Part I: A study of bio-mimetic monoglycerides behavior at the squalene-water interface by the “pendant drop” method in a static mode. J Dispers Sci Technol. 2006; 27: 799-810.
  • Kostyuk V, Potapovich A, Stancato A, De Luca C, Lulli D, Pastore S, Korkina L Photo-Oxidation Products of Skin Surface Squalene Mediate Metabolic and Inflammatory Responses to Solar UV in Human Keratinocytes. PLOS One. 2012; 7: e44472.
  • Ryu A, Arakane K, Koide C, Arai H, Nagano T. Squalene as a target molecule in skin hyperpigmentation caused by singlet oxygen. Biol Pharm Bull. 2009; 32: 1504-1509.
  • Fang JY, Fang CL, Liu CH, Su YH. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm. 2008; 70: 633-6
  • Saint-Leger D, Bague A, Cohen E, Chivot M. A possible role for squalene in the pathogenesis of acne I. In vitro study of squalene oxidation. Br J Dermatol. 1986; 114: 535-542.
  • Richter E, Fichtl B, Schafer SG. Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats.Chem Biol Interact.1982; 40: 335-344.
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  • Owen RW, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. Phenolic compounds and squalene in olive oils: the concentration and antioxidant potential of total phenols, simple phenols, secoiridoids, lignansand squalene. Food Chem Toxicol. 2000; 38: 647-659.
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  • Ohkuma T, Otagiri K, Tanaka S, Ikekawa T. Intensification of host’s immunity by squalene in sarcoma 180 bearing ICR mice. J Pharmacobiodyn. 1983; 6: 148-151.
Toplam 93 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Articles
Yazarlar

Fatma Esra Güneş

Yayımlanma Tarihi 30 Ocak 2014
Gönderilme Tarihi 30 Ocak 2014
Yayımlandığı Sayı Yıl 2013 Cilt: 3 Sayı: 4

Kaynak Göster

APA Güneş, F. E. (2014). Doğal bir antioksidan olarak skualenin medikal kullanımı. Clinical and Experimental Health Sciences, 3(4), 220-228.
AMA Güneş FE. Doğal bir antioksidan olarak skualenin medikal kullanımı. Clinical and Experimental Health Sciences. Şubat 2014;3(4):220-228.
Chicago Güneş, Fatma Esra. “Doğal Bir Antioksidan Olarak Skualenin Medikal kullanımı”. Clinical and Experimental Health Sciences 3, sy. 4 (Şubat 2014): 220-28.
EndNote Güneş FE (01 Şubat 2014) Doğal bir antioksidan olarak skualenin medikal kullanımı. Clinical and Experimental Health Sciences 3 4 220–228.
IEEE F. E. Güneş, “Doğal bir antioksidan olarak skualenin medikal kullanımı”, Clinical and Experimental Health Sciences, c. 3, sy. 4, ss. 220–228, 2014.
ISNAD Güneş, Fatma Esra. “Doğal Bir Antioksidan Olarak Skualenin Medikal kullanımı”. Clinical and Experimental Health Sciences 3/4 (Şubat 2014), 220-228.
JAMA Güneş FE. Doğal bir antioksidan olarak skualenin medikal kullanımı. Clinical and Experimental Health Sciences. 2014;3:220–228.
MLA Güneş, Fatma Esra. “Doğal Bir Antioksidan Olarak Skualenin Medikal kullanımı”. Clinical and Experimental Health Sciences, c. 3, sy. 4, 2014, ss. 220-8.
Vancouver Güneş FE. Doğal bir antioksidan olarak skualenin medikal kullanımı. Clinical and Experimental Health Sciences. 2014;3(4):220-8.

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